Mannose-resistantProteus-like andP. mirabilisfimbriae have specific and additive roles inP. mirabilisurinary tract infections

Zunino, Pablo; Sosa, Vanessa; Schlapp, Geraldine; Allen, Andrew G.; Preston, Andrew; Maskell, Duncan J.

doi:10.1111/j.1574-695x.2007.00285.x

Cited by 28 publications

(29 citation statements)

References 27 publications

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“…The exact virulence role of PMF fimbriae is unclear (NIELUBOWICZ & MOBLEY 2010). ZUNINO et al (2007) by using P. mirabilis pmfA/mrpA-D mutant showed the specific and additive roles of MR/P and PMF fimbriae in UTI caused by these bacteria. NAF fimbriae, earlier known as UCA fimbriae, allow bacteria to colonize uroepithelial cells (WRAY et al 1986).…”

Section: Pathogenicitymentioning

confidence: 99%

Proteus sp. – an opportunistic bacterial pathogen – classification, swarming growth, clinical significance and virulence factors

et al. 2012

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The genus Proteus belongs to the Enterobacteriaceae family, where it is placed in the tribe Proteeae, together with the genera Morganella and Providencia. Currently, the genus Proteus consists of five species: P. mirabilis, P. vulgaris, P. penneri, P. hauseri and P. myxofaciens, as well as three unnamed Proteus genomospecies. The most defining characteristic of Proteus bacteria is a swarming phenomenon, a multicellular differentiation process of short rods to elongated swarmer cells. It allows population of bacteria to migrate on solid surface. Proteus bacteria inhabit the environment and are also present in the intestines of humans and animals. These microorganisms under favorable conditions cause a number of infections including urinary tract infections (UTIs), wound infections, meningitis in neonates or infants and rheumatoid arthritis. Therefore, Proteus is known as a bacterial opportunistic pathogen. It causes complicated UTIs with a higher frequency, compared to other uropathogens. Proteus infections are accompanied by a formation of urinary stones, containing struvite and carbonate apatite. The virulence of Proteus rods has been related to several factors including fimbriae, flagella, enzymes (urease - hydrolyzing urea to CO2 and NH3, proteases degrading antibodies, tissue matrix proteins and proteins of the complement system), iron acqusition systems and toxins: hemolysins, Proteus toxin agglutinin (Pta), as well as an endotoxin - lipopolysaccharide (LPS). Proteus rods form biofilm, particularly on the surface of urinary catheters, which can lead to serious consequences for patients. In this review we present factors involved in the regulation of swarming phenomenon, discuss the role of particular pathogenic features of Proteus spp., and characterize biofilm formation by these bacteria.

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Section: Pathogenicitymentioning

confidence: 99%

Proteus sp. – an opportunistic bacterial pathogen – classification, swarming growth, clinical significance and virulence factors

et al. 2012

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“…Among these, the best studied is the mannose-resistant Proteus-like (MR/P) fimbria, which has been shown to be an important virulence factor that contributes to colonization of the urinary tract in a murine model of infection (17), as well as affecting the localization of bacteria within the bladder (18). In fact, all mutants defective in MR/P fimbria assembly tested thus far are attenuated for virulence in experimental UTIs (19)(20)(21)(22). Expression of MR/P fimbriae undergoes phase variation: the mrp promoter contains an invertible element flanked by inverted repeat sequences, and the orientation of this element strictly regulates transcription of the fimbrial operon (20,23).…”

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confidence: 99%

Transcriptional Analysis of the MrpJ Network: Modulation of Diverse Virulence-Associated Genes and Direct Regulation of mrp Fimbrial and flhDC Flagellar Operons in Proteus mirabilis

et al. 2015

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The enteric bacterium Proteus mirabilis is associated with a significant number of catheter-associated urinary tract infections (UTIs). Strict regulation of the antagonistic processes of adhesion and motility, mediated by fimbriae and flagella, respectively, is essential for disease progression. Previously, the transcriptional regulator MrpJ, which is encoded by the mrp fimbrial operon, has been shown to repress both swimming and swarming motility. Here we show that MrpJ affects an array of cellular processes beyond adherence and motility. Microarray analysis found that expression of mrpJ mimicking levels observed during UTIs leads to differential expression of 217 genes related to, among other functions, bacterial virulence, type VI secretion, and metabolism. We probed the molecular mechanism of transcriptional regulation by MrpJ using transcriptional reporters and chromatin immunoprecipitation (ChIP). Binding of MrpJ to two virulence-associated target gene promoters, the promoters of the flagellar master regulator flhDC and mrp itself, appears to be affected by the condensation state of the native chromosome, although both targets share a direct MrpJ binding site proximal to the transcriptional start. Furthermore, an mrpJ deletion mutant colonized the bladders of mice at significantly lower levels in a transurethral model of infection. Additionally, we observed that mrpJ is widely conserved in a collection of recent clinical isolates. Altogether, these findings support a role of MrpJ as a global regulator of P. mirabilis virulence. Bacterial pathogens utilize a myriad of complex regulatory networks to adapt gene expression in response to environmental cues encountered in the host. Trying to walk a fine balance of avoiding detection by the host immune system, while ensuring acquisition of all essential nutrients and promoting growth, bacteria employ transcriptional and posttranscriptional strategies to combat the host's defenses. A prominent example is the specific induction of iron and zinc uptake systems during infection, regulated by Fur and Zur, respectively, which allows pathogens to gain access to these essential transition metals in the restricted host environment (1, 2).Urinary tract infections (UTIs) are among the most common bacterial infections (3), presenting a significant public health burden amounting to annual costs of about 3.5 billion dollars in the United States alone (4). Although Proteus mirabilis causes a relatively small proportion of UTIs in healthy individuals, it is a common cause of cystitis and pyelonephritis in individuals with indwelling catheters or anatomical abnormalities of the urinary tract (4, 5).UTIs occur almost exclusively in an ascending route, meaning that bacteria of fecal origin gain entry to the bladder via the urethra and then spread to the kidneys via the ureters (4). Initially, bacteria adhere to host epithelial cells via proteinaceous supramolecular structures referred to as fimbriae (or pili) (6), which allow pathogens to withstand the mechanical flow of urine (5)...

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“…Four of these 17 operons have individually been linked to virulence in a murine model of infection (11)(12)(13)(14)(15)(16). Mannose-resistant Proteus-like (MR/P) fimbriae, the major adhesin produced during infection, contribute to bladder colonization (16).…”

mentioning

confidence: 99%

Distinct Residues Contribute to Motility Repression and Autoregulation in the Proteus mirabilis Fimbria-Associated Transcriptional Regulator AtfJ

et al. 2016

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Proteus mirabilis contributes to a significant number of catheter-associated urinary tract infections, where coordinated regulation of adherence and motility is critical for ascending disease progression. Previously, the mannose-resistant Proteus-like (MR/P) fimbria-associated transcriptional regulator MrpJ has been shown to both repress motility and directly induce the transcription of its own operon; in addition, it affects the expression of a wide range of cellular processes. Interestingly, 14 additional mrpJ paralogs are included in the P. mirabilis genome. Looking at a selection of MrpJ paralogs, we discovered that these proteins, which consistently repress motility, also have nonidentical functions that include cross-regulation of fimbrial operons. A subset of paralogs, including AtfJ (encoded by the ambient temperature fimbrial operon), Fim8J, and MrpJ, are capable of autoinduction. We identified an element of the atf promoter extending from 487 to 655 nucleotides upstream of the transcriptional start site that is responsive to AtfJ, and we found that AtfJ directly binds this fragment. Mutational analysis of AtfJ revealed that its two identified functions, autoregulation and motility repression, are not invariably linked. Residues within the DNA-binding helix-turn-helix domain are required for motility repression but not necessarily autoregulation. Likewise, the C-terminal domain is dispensable for motility repression but is essential for autoregulation. Supported by a three-dimensional (3D) structural model, we hypothesize that the C-terminal domain confers unique regulatory capacities on the AtfJ family of regulators. IMPORTANCEBalancing adherence with motility is essential for uropathogens to successfully establish a foothold in their host. Proteus mirabilis uses a fimbria-associated transcriptional regulator to switch between these antagonistic processes by increasing fimbrial adherence while simultaneously downregulating flagella. The discovery of multiple related proteins, many of which also function as motility repressors, encoded in the P. mirabilis genome has raised considerable interest as to their functionality and potential redundancy in this organism. This study provides an important advance in this field by elucidating the nonidentical effects of these paralogs on a molecular level. Our mechanistic studies of one member of this group, AtfJ, shed light on how these differing functions may be conferred despite the limited sequence variety exhibited by the paralogous proteins.T ranscriptional regulation in response to environmental cues, including temperature and nutrient availability, is critical to allow bacteria to adapt to their surroundings. The advent of whole-genome sequencing has led to the discovery that some pathogenic bacteria devote as much as 10% of their genome to regulatory systems, such as transcription factors, allowing for the appropriate protective or adaptive response to new environments (1, 2).Urinary tract pathogens, such as the Gram-negative enterobacterium Proteu...

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Mannose-resistantProteus-like andP. mirabilisfimbriae have specific and additive roles inP. mirabilisurinary tract infections

Cited by 28 publications

References 27 publications

Proteus sp. – an opportunistic bacterial pathogen – classification, swarming growth, clinical significance and virulence factors

Proteus sp. – an opportunistic bacterial pathogen – classification, swarming growth, clinical significance and virulence factors

Transcriptional Analysis of the MrpJ Network: Modulation of Diverse Virulence-Associated Genes and Direct Regulation of mrp Fimbrial and flhDC Flagellar Operons in Proteus mirabilis

Distinct Residues Contribute to Motility Repression and Autoregulation in the Proteus mirabilis Fimbria-Associated Transcriptional Regulator AtfJ

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